Mania, treatment

Ziprasidone is approved for the treatment of schizophrenia and acute mania. For patients with schizophrenia, ziprasidone is usually started at a dosage of 20-40 mg twice a day. In medically healthy, nonelderly patients, the dose can be rapidly titrated over 2-A days to a typical therapeutic dosage of 60-80 mg twice a day. For patients with acute mania, treatment should be initiated at 40 mg twice... 

Baldessarini RJ, Hennen J, Wilson M, et al. Olanzapine versus placebo in acute mania treatment responses in subgroups. J CUn Psychopharmacol 2003 23 370-376. 

Swann AC, Bowden CL, Morris D et al. Depression during mania. Treatment response to lithium or divalproex. Arch Gen Psychiatry 1997 54 37. 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

G. L. Gessa, W. Fratta, L. Pani, and G. Serra, Depression and Mania From Neurohiology to Treatment, Lippincott-Raven, Hagerstown, Md., 1995, p. 1. 

Drug treatment is a vital part of the management of bipolar disorder, both during episodes of depression or mania and as prophylaxis thereafter. Patients require explanation and education about the illness and about the treatments available, in order to be able to make informed choices and to avail themselves of the appropriate options fot treatment. 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

The first mood stabilizer was lithium (its antimanic action being discovered in 1948) more recently the anticonvulsant drugs carbamazepine and valproate have been found to be effective in acute mania. Unfortunately these mood stabilizers are only successful in controlling mania to a limited extent and few patients are well enough to leave hospital at the end of 3 weeks of treatment using these drugs as monotherapy. It is increasingly common for combination treatment to be advocated, in which an antipsychotic dmg is combined with lithium or an anticonvulsant. 

Crucial factors affecting overall cost are the responsiveness to medication (for example, less than 70% of patients are lithium responders ), adherence to recommended treatment, and adverse events resulting from medication. A particular hazard of lithium treatment is the risk of rapid re-emergence of mania, which occurs in up to 50% of patients if the dmg is abruptly discontinued (see Cookson, 1997). Disappointingly, it has not been found that the introduction of widespread treatment with lithium has been associated with a reduction in the number of patients admitted and discharged from hospital with a diagnosis of mania. In order to achieve the best result with the available... 

Depression and mania are both affective disorders but their symptoms and treatments are quite distinct. Mania is expressed as heightened mood, exaggerated sense of self-worth, irritability, aggression, delusions and hallucinations. In stark contrast, the most obvious disturbance in depression is melancholia that often co-exists with behavioural and somatic changes (Table 20.1). Some individuals experience dramatic mood swings between depression and mania. This is known as "bipolar disorder which, like mania itself, is treated with lithium salts or neuroleptics. 

Light therapy is an alternative treatment for depression associated with seasonal (e.g., winter) exacerbations. Possible side effects include eye strain, headache, insomnia, and hypo-mania.16,17 Also, potentially vulnerable patients, such as those with photosensitivity or a history of skin cancer, should be evaluated carefully prior to therapy.16... 

Electroconvulsive therapy (ECT) is the application of prescribed electrical impulses to the brain for the treatment of severe depression, mixed states, psychotic depression, and treatment-refractory mania in patients who are at high risk of suicide. It also may be used in pregnant women who cannot take carbamazepine, lithium, or divalproex. 

Fourth, if response is inadequate, consider ECT for mania with psychosis or catatonia 6 or add clozapine for treatment-refractory illness Fifth, if response is inadequate, consider adding adjunctive therapies8... 

Electroconvulsive therapy (ECT) is used for severe mania or depression during pregnancy and for mixed episodes prior to treatment, anticonvulsants, lithium, and benzodiazepines should be tapered off to maximize therapy and minimize adverse effects. 

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

Table 36-4 includes a summary of current drug therapy for bipolar disorder. An algorithm for treatment of bipolar mania is shown in Table 36-2. 

Sprinkle capsule 15, 25 mg Atypical Antipsychotics FDA approved for use in bipolar disorder Aripiprazole Abilify Tablets 5, 10, 15, Dosage should be slowly increased to minimize adverse effects (e.g., 25 mg at bedtime for 1 week, then 25-50 mg/day increments at weekly intervals) 10-30 mg/day once daily acute treatment of mania or mixed episodes due to lack of efficacy used as an adjunctive agent with established mood stabilizers Use as monotherapy or in... 

Olanzapine Zyprexa 20, 30 mg Tablets 2.5, 5, 7.5, 10, 5-20 mg/day in 1 or 2 doses combination with lithium or valproate for the acute treatment of mania or mixed states for bipolar I disorder. Olanzapine and aripiprazole are approved for relapse prevention as well as for acute therapy... 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Lamotrigine is effective for the maintenance treatment of bipolar disorder. It is more effective for depression relapse prevention than for mania relapse. Its primary limitation as an acute treatment is the time required for titration to an effective dosage. In addition to maintenance monotherapy, it is sometimes used in combination with lithium or divalproex, although combination with divalproex increases the risk of rash, and lamotrigine dosage adjustment is required.37... 

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

Comorbid conditions must be addressed in order to maximize desired outcomes. For comorbid bipolar disorder and attention-deficit/hyperactivity disorder when stimulant therapy is indicated, treatment of mania is recommended before starting the stimulant in order to avoid exacerbation of mood symptoms by the stimulant. 

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